Multigenerational Study Research Articles

Body and organ weight, sperm acrosomal status and reproduction after genistein and diethylstilbestrol treatment of CD1 mice in a multigenerational study

The effect of genistein (GEN) and diethylstilbestrol (DES) on body weight, weight of different organs, sperm acrosomal status and in vivo fertility of CD1 mice was tested in a multigenerational study. The adult parental generation of mice and F1 and F2 generations were exposed to selected drugs for all their life. GEN had effect on different body parameters of 30-day-old mice, but not of adult mice in the first generation. Contrary to that, treatment by DES had a strong effect on body weight, other body parameters and on the levels of serum hormones. In the first generation only sterile pairs of mice were observed. Monoclonal antibody against mouse intra-acrosomal sperm protein was used for analysis of the acrosome state and as biomarkers of sperm damage. In the control groups, about 93% of acrosome-reacted sperm was found, acrosome staining decreased to 78–84% ( P<0.01). However, the GEN had no effect on fertility of CD1 mice. On the other hand, the fertility of mice exposed to DES was disrupted, especially in the first generation.

Replicated Findings and Future Directions for Intergenerational Studies: Closing Comments

This commentary summarizes findings from four papers that set out to replicate, albeit not with identical measures or sampling criteria, research on several questions in the multigenerational study of antisocial behavior by children and child-rearing strategies by parents. The weight of the evidence from our studies indicates some degree of intergenerational continuity in behavior. We observed that adjacent generations G1 and G2 are similar with respect to their styles of parenting and that adjacent generations G2 and G3 are similar with respect to antisocial behavior. In addition, the G2 parent's parenting style plays an important role in mediating or transferring the risk of antisocial behavior across the generations. Implications and directions for future research are discussed.

Predictors of grandmother participation in a multigenerational study.

Results of a growing body of literature regarding multigenerational relationships indicate that grandparents directly and indirectly influence their grandchildren's development. However, multiple generations have been difficult to assemble for research purposes, with refusal rates ranging from 40 percent to over 80 percent. Despite difficulties in obtaining information from more than one generation of family members, data examining potential biases in the selection of participants have rarely been reported. The present study explored predictors of grandmother participation in a multigenerational study with 84 mothers, 84 infants, and 52 maternal grandmothers. Results indicated that grandmothers were less likely to participate in the study when grandchildren experienced preterm birth and when mothers reported less family of origin support. However, grandmothers who participated in the study reported high levels of intergenerational involvement and contact with daughters and grandchildren.

Women with Family History of Breast Cancer Have Added Risk with Pill Use

A multigenerational family study conducted between 1991 and 1996 revealed that women whose sisters or mothers have had breast cancer are at increased risk of developing the disease. The study also suggests that their risk is further elevated if they use oral contraceptives. Overall among sisters and daughters of women with breast cancer those who had ever used the pill had 3.3 times the breast cancer risk of those who had never used this method; the relative risk increased if breast or ovarian cancer occurred more than once among blood relatives. Moreover the elevated risk associated with pill use appeared only among women who had taken oral contraceptives during or before 1975; after that year all oral contraceptives introduced to the market contained less than 50 mcg of estrogen.

Interrelationships Among Inbreeding Depression, Plasticity in the Self-incompatibility System, and the Breeding System of Campanula rapunculoides L. (Campanulaceae)

Abstract The evolution of breeding systems in plants is often viewed as a balance between the adverse consequences of selfing (inbreeding depression and the loss of opportunities to sire seeds on conspecifics) and the benefits of selfing (a genetic transmission advantage and reproductive assurance when cross pollen limits seed production). In this paper we examine the genetic and environmental causes of variation in the expression of self-incompatibility (SI) in Campanula rapunculoides and explore the consequences of this variation on the breeding system. Campanula rapunculoides has an S-RNase based SI system similar to that described in the Solanaceae. However, our studies of plants from two natural populations have revealed that the flowers of most individuals are self-incompatible when they first open but become more self fertile as the flowers age. Moreover, when both cross and self pollen are deposited onto the stigmas of older flowers, the cross pollen tubes grow faster and sire a disproportionate number of the seeds. In short, self-fertilization occurs only after most opportunities for outcrossing have occurred. We also found that there is significant heritable genetic variation in the population for the strength of SI in young and old flowers and for the amount of breakdown in SI indicating that natural selection could operate on the strength of SI and its breakdown. In a multigenerational study, we used controlled crosses to create families of plants with a range of inbreeding coefficients (0, 0.25, 0.5 and 0.75). We found that fitness declined significantly over the range of inbreeding coefficients and that the decline in fitness was less for families derived from weak SI phenotypes. Consequently, it is only advantageous for C. rapunculoides to produce selfed seed when seed production is limited by the availability of cross pollen. Because of plasticity in the SI system,C. rapunculoides has a breeding system that combines the best of both worlds.

Transmission of Risk Factors across Three Generations

The present study examined the association between the parent-grandmother relationship, the parenting of toddlers, and toddlers' anger. Parent-grandmother relations were assessed when the parents were adolescents. Patient-toddler relations were examined when the toddlers were two years of age. The sample consists of 185 2-yr-old toddlers, one of the parents of each toddler, and the corresponding grandmother of each toddler. The findings support our hypothesis that there would be an indirect effect of the grandmothers' personalities and child-rearing practices on their grandchildren through the influence of the grandmothers on the parents. The influence of both the grandmothers' and the parents' smoking behaviors on the toddlers' anger was mediated by their child-rearing practices. The significance of the findings from a multigenerational study are discussed with reference to incorporating them into prevention programs. The findings are consistent with the notion of the intergenerational transmission of risk factors--from grandparents to parents to toddlers.

The role of grandparents when parents part or die: some reflections on the mythical decline of the extended family

Belief that the extended family is in terminal decline has proved to be a remarkably persistent myth. It is currently being revived as a result of recent statistical trends. The belief has been closely connected to sociological enquiries undertaken over the course of the century. The validity of the belief, and in particular the significance of grandparents within the extended family, is explored in two sets of life story interviews recently undertaken with adults in Britain; one set are people in their thirties who had become step-children, and the second set participants in a multi-generational study of social mobility. The analysis addresses questions of contact after parental loss, sources of support within the family, the involvement of grandparents, the importance of co-residence, conflict, emotional closeness and communication within a family.

Effects of 17 beta-estradiol on serum hormone concentrations and estrous cycle in female Crl:CD BR rats: effects on parental and first generation rats.

The recently passed Food Quality Protection Act of 1996 requires the U.S. EPA to implement screening strategies for endocrine active compounds (EACs) within the next 2 years. Interpreting results from screening tests is complicated by the absence of traditional dietary rodent bioassay data with model estrogenic compounds such as 17 beta-estradiol. Thus, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to: (1) provide such baseline data; (2) set dose levels for multigeneration reproduction and combined chronic toxicity/oncogenicity studies; and (3) evaluate various mechanistic/biochemical endpoints for inclusion in these follow-up studies. The current article describes the effects of dietary administration of 0, 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol on the serum hormone concentrations and estrous cyclicity of female Crl:CD BR rats and evaluates a sampling strategy for measuring serum hormone levels in cycling female rats. Serum hormones were measured at three time points during a 90-day dietary exposure (1 week, 28 days, and 90 days) and in the F1 generation rats on postnatal day 98. Over the course of the 90-day feeding study for the P1 generation and from postnatal days 21 to 98 for the F1 generation, the estrous cycle was monitored daily in 10 rats/group. In P1 generation rats, dietary administration of 2.5, 10, and 50 ppm 17 beta-estradiol produced a dose-dependent increase in serum estradiol (E2) concentrations at all time points. In contrast, administration of 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol produced a dose-dependent decrease in serum progesterone (P4) concentrations on test day 90, which correlated with an absence of corpora lutea and ovarian atrophy. At 10 and 50 ppm 17 beta-estradiol, serum luteinizing hormone (LH) concentrations were consistently decreased at all time points and were decreased at 2.5 ppm on test day 90. Serum prolactin (PRL) concentrations were increased at 50 ppm 17 beta-estradiol on test day 90. Serum follicle stimulating hormone (FSH) concentrations were either similar to the control levels or minimally changed at all time points. No F1 generation rats were produced at 10 or 50 ppm 17 beta-estradiol. In F1 generation rats, serum E2 concentrations were increased and P4 concentrations were decreased at a dietary concentration of 2.5 ppm 17 beta-estradiol, while serum concentrations of LH, FSH, and PRL were similar to the control. Dietary administration of 17 beta-estradiol at concentrations of 2.5 (both generations) and 10 and 50 ppm (P1 generation only) produced marked effects on the estrous cycle: decreased number of cycles, increased mean cycle length, and decreased number of normally cycling rats. The estrous cyclicity of rats fed 2.5 ppm 17 beta-estradiol appeared more severely affected in rats of the F1 generation than in rats of the P1 generation. Whether this increase in severity is related to an in utero exposure and/or greater mean daily intake of 17 beta-estradiol in the F1 generation rats in the postnatal period is unclear. Another goal of this study was to evaluate whether a single time point sampling strategy using cycling female rats could be used to detect compound-related changes in serum hormone concentrations. In evaluating a sampling strategy for measuring serum hormone levels, it appears that detection of compound-related alterations in serum hormone concentrations can be best detected by sampling during diestrus. Since the stage of the cycle dramatically influences hormone concentrations, large sample sizes (n = 50) are needed if serum hormone measurements are not matched with the stage of the cycle. The data indicate that this strategy of measuring serum hormone concentrations has utility in detecting compound-related effects within the confines of a traditional guideline study (subchronic, chronic, or multigenerational reproduction study).

Effects of endophyte consumption on food intake, growth, and reproduction in prairie voles

Grasses infected with fungal endophytes are known to deter herbivores. Athough ingestion of infected plant tissues has detrimental effects on insects, birds, domestic livestock, and laboratory rodents, little is known about the consequences of endophyte consumption for wild rodent consumers. This multigenerational study investigated how consumption of tall fescue (Festuca arundinacea) seeds infected with the endophytic fungus Acremonium coenophialum affects prairie voles (Microtus ochrogaster). Breeding pairs were fed one of three base diets: laboratory rodent chow (C; control diet), 50% uninfected tall fescue seeds plus 50% chow (E-), or 50% endophyte-infected seeds plus 50% chow (E+). In the first generation, the E+ diet suppressed food and water intake, growth rates, and reproductive success, so no voles fed on the E+ diet could be followed in the second generation. In general, voles of the two generations performed similarly on the C and E- diets. Our findings show that prairie voles are sensitive to the presence of endophytes, or associated alkaloids, in their diets, and suggest that free-ranging voles avoid consuming endophyte-infected plant tissues if other foods are available.

Affirmative Action and Elite Formation: An Untouchable Family History

A multigenerational case study of an elite Untouchable family reveals the problems of integration, passing, and cultural affirmation in the development and democratization process. As a nonvisible minority it is possible to facilitate integration in Indian urban areas by hiding caste, while affirmative action programs facilitate upward mobility at the cost of having to proclaim Untouchable caste identity. These contradictory imperatives illustrate the difficulties facing elite Untouchables in achieving emancipation.

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A multigenerational study on the correlation of values and advance directives.

The development of the Values History instrument for use in advance directive decision making has raised the question of the importance of values in eliciting advance directives. This pilot study examines the relationship between the domains of values and advance directives drawn from the Values History in three generation intrafamily triads. Significant correlations between values and advance directives were found primarily within the youngest generation. Results reveal a relatively high familiarity by the participants of the various established forms of advance directives. Also, a significant percentage of parents and grandparents was found to have signed some form of advance directive.

A longitudinal study of offspring born to methadone-maintained women. I. Design, methodology, and description of women's resources for functioning.

In order to examine alternatives to the hypothesis that any lasting damage to a child is caused by the direct toxic effects of fetal exposure to methadone, we designed a longitudinal, multigenerational study of the offspring of methadone-maintained women. We collected extensive data on both parents and children, hypothesizing that drugs can affect infants through a variety of causal routes. We have used a method of data analysis, POSAC, that retains the identity of individual children and families, and enables us to look at patterns of individuals' behavior over time and identify meaningful subgroups of individuals. We collected extensive information from 18 methadone-maintained and 24 comparison women. During the last trimester of pregnancy, we interviewed the women about their education, families, lifestyles, drug use, and health histories; we also assessed their psychiatric functioning and IQ's. We found that as a group the methadone-maintained women were more likely to receive public assistance, to evidence psychiatric dysfunctioning, and to be less educated (although showing no statistical difference in IQ's) than were comparison women. Similar to comparison women, two-thirds of methadone-maintained women were involved in stable relationships with male partners. The methadone-maintained women appeared committed to their methadone treatment and, in general, viewed their pregnancies in positive terms. Although as a group the methadone-maintained women possessed poorer resources for maternal functioning than the comparison group, about half the methadone-maintained women possessed resources at least adequate for maternal functioning.

Family Development in Three Generations.

Family Development in Three Generations is an unusual kind of multigenerational gathering-the result of a massive, in-depth research effort. It is based upon Hill's personal interviews conducted with over 300 families during the course of a year. The discussion results from these interviews, from the statistical information that they produced, and from Hill's consultation with fi ve other fellow researchers. This scholarly contribution to the family fi eld thoroughly analyzes the complexities of the modifi ed generational network. As a multi-generational study, it is pervaded by the vigorous spirit that usually characterizes such research.

The effects of long-term feeding of DDT to BALB-c mice.

AbstractA multigenerational study on the long‐term effects of three dose levels of DDT (2, 20 and 250 ppm in the diet) and one dose level of N‐nitrosodimethylamine (DMN) (0.0003% in the drinking water) was started in 1968. Each treatment was administered to two separate colonies of BALB/c mice. Treatment of parent mice started at 4‐5 weeks of age. The results observed in the first two generations are presented in this report. Survival in males was poor because of fighting. In females, the highest dose level of DDT produced liver‐cell tumours in 44% of the parent mice and 74% of the first generation mice, whereas no liver‐cell tumours were found in mice given the control diet, or lower dietary concentrations of DDT. Liver cell tumours did not give metastases, but grew after transplantation to syngeneic mice. The ability of DDT to induce liver‐cell tumours was identical in both colonies of mice given 250ppm DDT. Malignant lymphomas occurred in about 50% of the mice in all colonies given 0, 2 or 20 ppm DDT. In one of the two colonies given 250ppm DDT, the incidence of malignant lymphomas was 14%, whereas in the other it was 36%. The incidence of lung adenomas was not affected by DDT treatment. Tumours at sites other than liver, lymphatic system and lungs were highest in control mice and lowest in mice given 250 ppm DDT. However, no linear dose‐response was found, and the decrease was more obvious in the parental than in the first generation. A study on the combinations of tumours in mice with more than one tumour and an analysis of litter distribution of liver‐cell tumour‐bearing mice did not reveal any particular trend in the distribution of liver‐cell tumours. The quantitative aspects of tumour induction by DDT in BALB/c mice are compared with data from previous studies in mice. DMN consistently produced lung adenomas, liver blood cysts and haemangioendotheliomas.